I continued watching the ONT “Empowering comprehensive sequencing at scale” session. The next speaker in this session was Brynja Sigurpalsdottir who spoke about large-scale methylation studies. They spoke about how base calling is used to detect methylation. The team sequenced 7,179 whole blood samples sequenced on 8906 PromethION R9.4 flowcells! Twenty-two samples were sequenced on 28 R10.4 flow cells. Methylation is being called for samples. The sample-to-sample comparison revealed consistency. The team identified bimodal methylation distribution. Quality filters can be used to enhance accuracy. All this work was published in a study and a second one in Nature Genetics. The team concluded that methylation-depleted sequences (MDS) can be used on phased samples. About forty percent were associated with a sequence variant. They then phased the RNA sequences from 896 samples. All of the methylation-depleted sequences were associated with mRNA expression differences. Additionally, the identified ASM-QTLs correspond to disease-associated variants. Sigurpalsdottir concluded that “the sequence variants is the primary driver of correlations between CpG methylation and gene expression.”
